Longitudinal follow-up of metformin treatment in Fragile X Syndrome

Panhaneath Seng; Federica Alice Maria Montanaro; Hazel Maridith Barlahan Biag; Maria Jimena Salcedo-Arellano; Kyoungmi Kim; Matthew Dominic Ponzini; Flora Tassone; Andrea Schneider; Leonard Abbeduto; Angela John Thurman; David Hessl; Francois V Bolduc; Sebastien Jacquemont; Sarah Lippé; Randi J Hagerman

doi:10.3389/fpsyg.2024.1305597

Longitudinal follow-up of metformin treatment in Fragile X Syndrome

Front Psychol. 2024 Jun 13:15:1305597. doi: 10.3389/fpsyg.2024.1305597. eCollection 2024.

Authors

Panhaneath Seng^#¹, Federica Alice Maria Montanaro^#^{2

3}, Hazel Maridith Barlahan Biag^{1

4}, Maria Jimena Salcedo-Arellano^{1

4}, Kyoungmi Kim^{1

5

6}, Matthew Dominic Ponzini^{1

5}, Flora Tassone^{1

7}, Andrea Schneider^{1

4}, Leonard Abbeduto^{1

8}, Angela John Thurman^{1

8}, David Hessl^{1

8}, Francois V Bolduc⁹, Sebastien Jacquemont^{10

11}, Sarah Lippé^{10

12}, Randi J Hagerman^{1

5}

Affiliations

¹ MIND Institute, University of California Davis Health System, Sacramento, CA, United States.
² Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
³ Department of Education, Psychology, Communication, University of Bari Aldo Moro, Bari, Italy.
⁴ Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA, United States.
⁵ Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, CA, United States.
⁶ Integrative Genetics and Genomics Graduate Group, University of California Davis, Davis, CA, United States.
⁷ Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, United States.
⁸ Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, United States.
⁹ Department of Pediatrics, Department of Medical Genetics, Women and Children Health Research Institute, University of Alberta, Edmonton, AB, Canada.
¹⁰ CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
¹¹ Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
¹² Department of Psychology, Université de Montréal, Montreal, QC, Canada.

^# Contributed equally.

Abstract

Introduction: Metformin has been used as a targeted treatment to potentially improve cognition and slow the typical IQ decline that occurs during development among individuals with fragile X syndrome (FXS). In this follow-up study, we are following the trajectory of IQ and adaptive behavior changes over 1 to 3 years in individuals with FXS who are clinically treated with metformin in an open label trial.

Method: Individuals with FXS ages 6 to 25 years (mean 13.15 ± 5.50) and nonverbal IQ mean 57.69 (±15.46) were treated for 1-3 years (1.88 ± 0.63). They all had a baseline IQ test using the Leiter-III non-verbal cognitive assessment and the Vineland-III adaptive behavior assessment before the start of metformin. Repeat Leiter-III and Vineland-III were completed after at least 1 year of metformin (500-1,000 mg/dose given twice a day).

Result: There were no significant changes in non-verbal IQ or in the adaptive behavior measurements at FDR < 0.05. The findings thus far indicate that both IQ and adaptive behavior are stable over time, and we did not see a significant decline in either measure.

Conclusion: Overall, the small sample size and short follow-up duration limit the interpretation of the effects of metformin on cognitive development and adaptive functioning. There is individual variability but overall for the group there was no significant decline in IQ or adaptive behavior.

Keywords: IQ; adaptive behavior; fragile X syndrome; longitudinal follow-up; metformin; treatment.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Azrieli Foundation and NICHD P50 HD103526 our Intellectual and Developmental Disability Research center grant.